MECHANISM OF ETHNIC DIFFERENCES IN PSYCHOTROPHIC RESPONSES

比较不同民族患者对精神药物的反应并探讨其差异的可能原因。决定反应的假设因素有：药物代谢肝酶系统的遗传差异、蛋白质结合和饮食影响。通过广泛的身体和实验室检查来评估波多黎各人、美洲原住民、非裔美国人、亚洲人、高加索人和西班牙人背景的受试者。调查将由两部分组成：第一部分将致力于药物遗传学和蛋白质结合，将在第一年开始，并在五年资助期间持续，而第二部分将研究饮食影响，并在第三年开始。研究结果将导致一系列药物遗传学工具的发展，这些工具可应用于临床环境，用于预测许多精神药物的药代动力学和作用，以及更好地了解环境和饮食对这些药物代谢酶活性的影响。初步结果表明，CYP2D6突变在白种人中最高，在亚洲人中最低。然而，非洲裔和墨西哥裔美国人的数据表明，2D6的祖先群体存在显著的混合。

To compare the response and explore potential reasons for differences in response to psychotropic medication in different ethnic groups. The factors hypothesized in determining response are: inherited differences in drug metabolizing liver enzyme systems, protein binding, and dietary influences. To evaluate subjects from Puerto Rican, Native American, African-American, Asian, Caucasian and Hispanic backgrounds with extensive physical and laboratory examinations. The investigation will be composed of two parts: part 1 will be devoted to pharmacogenetics and protein binding and will start in year one and continue for the duration of the five year grant, while part II will address dietary influences and start in the third year. Results will lead to the development of a panel of pharmacogenetic tools that can be applied in clinical settings for predicting the pharmacokinetics and effects of many psychotropics as well as a better understanding of environment and diets in the activity of these drug metabolizing enzymes. Preliminary results indicate mutations of CYP2D6 as highest in Caucasians and lowest in Asians. Data on African and Mexican-Americans, however, suggest significant intermixing of ancestral groups for 2D6.